title: Limb ischemic preconditioning mitigates lung injury induced by haemorrhagic shock/resuscitation in rats.
abstract: OBJECTIVE
  Haemorrhagic shock and subsequent resuscitation induce acute lung injury. We elucidated whether bilateral lower limb ischemic pre-conditioning (IP) could mitigate lung injury in haemorrhagic shock/resuscitation rats. The role of heme oxygenase-1 (HO-1) was also elucidated.
  
  
  METHODS
  Adult male rats were randomized to receive haemorrhagic shock/resuscitation (HS), HS plus IP, or HS plus IP plus the HO-1 inhibitor tin protoporphyrin (SnPP) (n = 12 in each group). Sham groups were employed simultaneously. For pre-conditioning, 3 cycles of limb IP (10 min ischemia followed by 10 min reperfusion) were performed immediately before haemorrhagic shock. Haemorrhagic shock (mean arterial pressure: 40-45 mmHg) was induced by blood drawing and maintained for 120 min. SnPP was injected 5 min before resuscitation. Shed blood/saline mixtures were re-infused to achieve resuscitation. After monitoring for another 8h, rats were sacrificed. Arterial blood gas and alveolar-arterial oxygen difference (lung function index), histology, polymorphonuclear leukocytes/alveoli ratio (leukocyte infiltration index), wet/dry weight ratio (water content index), inflammatory molecules (e.g., chemokine, cytokine, prostaglandin E(2)), and malondialdehyde (lipid peroxidation index) assays were preformed.
  
  
  RESULTS
  Haemorrhagic shock/resuscitation induced significant lung function alterations and significant increases in leukocyte infiltration, water content, inflammation, and lipid peroxidation in lungs. Histological analysis confirmed that haemorrhagic shock/resuscitation caused marked lung injury. Limb IP significantly mitigated the adverse effects of haemorrhagic shock/resuscitation. Moreover, the protective effects of limb IP were reversed by SnPP.
  
  
  CONCLUSIONS
  Limb IP mitigates lung injury in haemorrhagic shock/resuscitation rats. The mechanisms may involve HO-1.
authors.affiliation: Department of Nursing, Mackay Medicine, Nursing and Management College, Taipei, Taiwan.
authors.forename: Woan-Ching
authors.initials: WC
authors.lastname: Jan
authors.forename: Cay-Huyen
authors.initials: CH
authors.lastname: Chen
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Tsai
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D006614:Hindlimb / Q000098:blood supply*; D019194:Ischemic Preconditioning; D055370:Lung Injury / Q000209:etiology* / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000009:adverse effects*; D012771:Shock, Hemorrhagic / Q000150:complications*